Language：English   Publisher：Molecular Genetics and Genomic Medicine  

Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, β-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

DOI： 10.1002/mgg3.2427

Web of Science

Scopus

PubMed

Language：English   Publisher：エルゼビア・ジャパン(株)  

Language：English   Publisher：Pediatric Neurology  

Background: Area postrema syndrome (APS), a rare childhood condition, manifests as intractable nausea and hiccups. APS has high diagnostic significance in neuromyelitis optica syndrome spectrum disorders (NMOSD) and can be the initial presentation of other critical diseases, including brainstem glioma. Methods: We described two representative cases of unrelated Japanese patients with APS. An etiologic evaluation, including a detailed intracranial neuroradiological examination and autoantibodies assessment, was performed. We also reviewed the literature focusing on the prognosis of pediatric APS symptoms. Results: A 14-year-old girl with aquaporin-4 antibody-positive NMOSD showed a good prognosis with immunotherapy, whereas another nine-year-old girl with irresectable medullary low-grade glioma had persistent symptoms for more than 10 years. All reported children aged >12 years were diagnosed with NMOSD, and patients aged <13 years showed heterogeneous etiologies. Conclusions: Distinctive time courses and neuroimaging features were key clinical findings for the diagnostic and therapeutic processes in these patients. This literature review highlights the wide spectrum and prognosis of pediatric-onset APS.

DOI： 10.1016/j.pediatrneurol.2023.12.010

Web of Science

Scopus

PubMed

Language：English   Publisher：International Journal of Molecular Sciences  

Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain. The patient had a high titer of anti-ZSCAN1 antibodies (348; reference range < 40), and the increased values did not decline after acute phase treatment. Other encephalitis-related antibodies, such as the anti-NDMA antibody, were not detected. The rapid progression from obesity onset to central hypoventilation with encephalitis warns about the severe consequences of early-onset ROHHAD syndrome. These data indicate that serial measurements of anti-ZSCAN1 antibodies might be useful for the diagnosis and estimation of disease severity. Further research is needed to determine whether it can predict the clinical course of ROHHAD syndrome and whether there is any difference in antibody production between patients with and without tumors.

DOI： 10.3390/ijms25052820

Web of Science

Scopus

PubMed

Language：English   Publisher：BMC Neurology  

Background: The systemic manifestations of coronavirus disease 2019 (COVID-19) include hyperinflammatory reactions in various organs. Recent studies showed evidence for the frequent involvement of central nervous system in affected patients; however, little is known about clinical features of cerebrovascular diseases in childhood-onset COVID-19. Case presentation: A 10-year-old boy recovered from SARS-CoV-2 infection without complication. On 14 days after infection, he presented with loss of consciousness. A head computed tomography detected a ruptured cerebral aneurysm at the left posterior cerebral artery accompanying subarachnoid hemorrhage (SAH). Immediate surgical intervention did not rescue the patient, resulting in the demise 7 days after admission. Serological and genetic tests excluded the diagnosis of vasculitis and connective tissue disorders. Retrospective analysis showed markedly higher levels of interleukin (IL)-1β, IL-6 and IL-8 in the cerebrospinal fluid than the serum sample concurrently obtained. A review of literature indicated that adult patients with COVID-19 have a risk for the later development of SAH during the convalescent phase of COVID-19. Conclusions: SAH is a severe complication of COVID-19 in children and adults who have asymptomatic cerebrovascular aneurysms. The markedly high levels of cytokines detected in the cerebrospinal fluid suggested that intracranial hyperinflammatory condition might be one of the possible mechanisms involved in the rupture of a preexisting cerebrovascular aneurysms.

DOI： 10.1186/s12883-023-03493-z

Web of Science

Scopus

PubMed

Language：English   Publisher：Pediatrics and Neonatology  

Background: To assess the performance of pediatric extracorporeal membrane oxygenation (ECMO) centers, outcomes were compared between metropolitan and other areas. Methods: A retrospective cohort study was conducted at three regional centers on Kyushu Island and the largest center in the Tokyo metropolitan area of Japan. The clinical outcomes of patients of ≤15 years of age who received ECMO during 2010–2019 were investigated, targeting the survival and performance at discharge from intensive care units (ICUs), using medical charts. Results: One hundred and fifty-five patients were analyzed (regional, n = 70; metropolitan, n = 85). Survival rates at ICU discharge were similar between the two areas (64%). In regional centers, deterioration of Pediatric Cerebral Performance Category (PCPC) scores were more frequent (65.7% vs. 49.4%; p = 0.042), but survival rates and ΔPCPC scores (PCPC at ICU discharge–PCPC before admission) improved in the second half of the study period (p = 0.005 and p = 0.046, respectively). Veno-arterial ECMO (odds ratio [OR], 3.00; p < 0.03), extracorporeal cardiopulmonary resuscitation (OR, 8.98; p < 0.01), and absence of myocarditis (OR, 5.47; p < 0.01) were independent risk factors for deterioration of the PCPC score. A sub-analysis of patients with acute myocarditis (n = 51), the main indicator for ECMO, revealed a significantly higher proportion of cases with deteriorated PCPC scores in regional centers (51.9% vs. 25.0%; p = 0.049). Conclusions: The survival rates of pediatric patients supported by ECMO in regional centers were similar to those in a metropolitan center. However, neurological outcomes must be improved, particularly in patients with acute myocarditis.

DOI： 10.1016/j.pedneo.2024.04.005

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Early Human Development  

Introduction: To establish actionable neonatal screening during the first month of life, we investigated critical diseases in seemingly healthy newborns discharged from birth hospitals. Methods: This retrospective study enrolled previously healthy full-term infants who visited our hospital, a tertiary hospital in Japan, from home between 5 and 28 days after birth from 2009 to 2018. Infants with known perinatal or congenital diseases, positive newborn screening results, or accidental injuries were excluded. Data were collected from electronic medical records, including principal diagnosis, clinical details, and prognosis at 18 months of age. Results: Ninety-seven (58 %) of 168 eligible neonates were admitted to the hospital, and 71 (42 %) were not. The median admission rate in patients with disease onset at ≤14 days after birth (80 %) was significantly higher than that in patients with disease onset at ≥15 days (42 %). Among 45 patients who received intensive medical care, 5 died and 10 developed neurodevelopmental sequelae. Four of 5 patients died by 100 days. Among 25 diseases treated in intensive care unit, 17 (68 %) diseases had a prevalence of <1 per 2000 live births. The commonly used diagnostic methods were imaging (n = 58, 35 %) and physical examination (n = 34, 20 %). Conclusion: Critical diseases due to rare and heterogeneous causes in ostensibly healthy newborns occurred predominantly in the first two weeks of life. Optimal newborn screening and health check-up protocols may benefit from the wide spectrum of life-threatening diseases occurring in home after birth.

DOI： 10.1016/j.earlhumdev.2023.105869

Web of Science

Scopus

PubMed

Publisher：Visual Journal of Emergency Medicine  

DOI： 10.1016/j.visj.2023.101649

Scopus

Language：English   Publisher：BMC Neurology  

Background: Intracranial aneurysms (ICA) rarely occur in children under 3 years of age. Little is known for neuroimaging parameters that predict survival and clinical outcomes of patients with ICA in early childhood. Case presentation: A 2-year-old girl showed intracranial hemorrhage due to a rupture of aneurysm at the middle cerebral artery. Quantitative measurements of ischemic damages on the head computed tomography (CT) marked an extremely low score of 2 points with modified Alberta Stroke Program Early CT Score (mASPECTS). She died 15 days after admission. In publications from 2021 to 2022, we found 21 children who were under 3 years of age at onset of ICA. None of them died, but two of three patients who had mASPECTS scores 0–8 showed developmental delay and/or epilepsy as neurological complications. Conclusion: Early CT findings are applicable for predicting survival and neurological outcomes of young children with intracranial hemorrhage.

DOI： 10.1186/s12883-022-03022-4

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English  

researchmap

Language：English   Publisher：European Journal of Clinical Nutrition  

Vitamin deficiencies are an emerging concern in the management of children with autism spectrum disorder (ASD). Particular attention is required for recognizing the variable signs caused by unbalanced food intakes. We herein report two patients with multiple vitamin deficiencies who needed critical care showing different prognoses. Patient 1 with ‘Shoshin’ beriberi presenting with cardiac arrest had thiamine deficiency developed severe neurological sequelae despite rapid vitamin supplementation. Patient 2, who had leg pain and a limping gait, showed a rapid recovery with intravenous infusion and tube feeding after being diagnosed with scurvy. A literature search revealed several children with ASD with critically ill thiamine deficiency, but few reports documented a life-threatening condition in the form of cardiac arrest at the onset. Considering the high observation rate of food selectivity in children with ASD, early intervention is required to prevent the exacerbation of vitamin deficiencies to severe neurological disabilities.

DOI： 10.1038/s41430-022-01170-x

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English  

researchmap

Language：English   Publisher：Journal of International Medical Research  

Objective: This study was performed to evaluate the correlation between parameters measured by bedside ultrasonography and detection of intracranial organic lesions in patients with impaired consciousness in an intensive care unit (ICU) setting. Methods: We retrospectively reviewed the medical records of patients who were admitted to our ICU from April 2017 to July 2019. Patients who underwent computed tomography or magnetic resonance imaging examination and measurement of the flow velocity of the carotid and intracranial arteries and the optic nerve sheath diameter by ultrasonography were selected for analysis. Results: In total, 64 patients were analyzed in this study. Of these, intracranial lesions were detected by computed tomography or magnetic resonance imaging in 17 (27%) patients. The left:right ratio of the end-diastolic velocity of the bilateral common carotid artery (CCA-ED ratio) and the pulsatility index of the middle cerebral artery (MCA-PI) were significantly higher in patients with than in those without intracranial lesions. The cut-off value of the CCA-ED ratio was 1.55 (sensitivity, 66.7%; specificity, 81.6%), and that of the MCA-PI was 1.21 (sensitivity, 57.1%; specificity, 76.7%). Conclusion: Bedside ultrasonography is useful for predicting intracranial lesions requiring therapeutic intervention in ICU patients with impaired consciousness.

DOI： 10.1177/03000605221119358

Web of Science

Scopus

PubMed

Language：English   Publisher：Pediatrics International  

DOI： 10.1111/ped.15018

Web of Science

Scopus

PubMed

Publisher：Clinical and Applied Thrombosis/Hemostasis  

Recombinant antithrombin gamma (rAT) is reported as an effective drug for patients with disseminated intravascular coagulation (DIC) in Japan. As the appropriate dose and targeted AT activity remain unknown, this study aimed to determine these aspects for sepsis-induced DIC. Thirty-one patients with septic shock and DIC with AT levels <70% were treated with rAT between May 2018 and December 2020. The recovery rates from DIC were 32.2% and 63.3% on day 3 and 5 post administration, respectively. Recovery and survival rates were significantly higher in patients who achieved AT activity ≥70% or 80% on day 3 post administration. Receiver operating characteristic curve analysis revealed that the cutoff values of post-treatment AT activity on day 3 for 28-day survival and 5-day recovery from DIC were 79.5% and 81.5%, respectively. Patients who did not achieve AT activity ≥80% on day 3 presented a lower base level of AT activity and lower dose supplementation. Our results suggest that targeted AT activity should be at least 70%, and ideally 80%, and sufficient doses to maintain this activity are required to achieve better outcomes.

DOI： 10.1177/10760296221135790

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clineuro.2021.106922

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-021-91628-y.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00467-020-04619-y

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12881-020-01019-9

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12185-019-02738-3

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.transproceed.2020.06.010

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1177/1129729820937133

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/PCC.0000000000001996

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12879-019-4082-4

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2018.10.012

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1177/1550059418786381

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jns.2018.10.007

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.eplepsyres.2018.04.006

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12941-018-0282-9

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ped.13432

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ajem.2017.06.011

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.braindev.2017.03.023

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jns.2016.09.018

Language：English   Publishing type：Research paper (scientific journal)  

Toxic shock syndrome (TSS) is a critical illness associated with toxin from Staphylococcus aureus. Despite recent advances in critical care, mortality remains high and additional effective therapy is required. We report an adolescent case of TSS successfully treated with direct hemoperfusion using polymyxin-B immobilized fiber (PMX-DHP). The patient with spina bifida also had ischial pressure ulcer, and developed TSS associated with methicillin-resistant S. aureus. Despite conventional treatment, the patient developed refractory shock, which was immediately improved with PMX-DHP. PMX-DHP has been widely used for the treatment of sepsis to remove circulating endotoxins produced by Gram-negative bacteria, but beneficial effects have also been reported for Gram-positive bacterial infection. To our knowledge, this is the first report on PMX-DHP for TSS in an adolescent patient, and we propose that PMX-DHP could be a new treatment strategy for severe TSS in children as well.

DOI： 10.1111/ped.13087

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.7883/yoken.JJID.2015.591

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00068-014-0478-4

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/pbc.20514

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2017.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：郡山   Country：Japan  

Event date： 2017.3

Language：Japanese  

Venue：札幌   Country：Japan  

Event date： 2016.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2016.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2016.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：富山   Country：Japan  

Event date： 2016.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大宮   Country：Japan  

Event date： 2016.6

Language：Japanese  

Venue：大牟田   Country：Japan  

Event date： 2014.6

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜   Country：Japan  

Event date： 2014.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋市   Country：Japan  

Event date： 2014.4

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：名古屋市   Country：Japan  

Event date： 2013.8 - 2013.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：福岡市   Country：Japan  

Event date： 2013.7

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2013.7

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：宮崎市   Country：Japan  

Event date： 2012.6

Presentation type：Symposium, workshop panel (public)  

Venue：熊本市   Country：Japan  

Event date： 2012.6

Presentation type：Oral presentation (general)  

Venue：神戸市   Country：Japan  

Event date： 2012.6

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2012.2 - 2012.3

Presentation type：Oral presentation (general)  

Venue：千葉   Country：Japan  

Event date： 2011.11

Venue：福島   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2011.10

Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2011.10

Presentation type：Oral presentation (general)  

Venue：福島   Country：Japan  

Event date： 2011.9

Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2011.8

Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：札幌市   Country：Japan  

Event date： 2011.6

Presentation type：Oral presentation (general)  

Venue：札幌市   Country：Japan  

Event date： 2010.9

Presentation type：Oral presentation (general)  

Venue：福岡県みやま市   Country：Japan  

Event date： 2010.6

Presentation type：Oral presentation (general)  

Venue：千葉市   Country：Japan  

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English  

Language：Japanese   Publishing type：Internal/External technical report, pre-print, etc.  

Language：Japanese   Publishing type：Internal/External technical report, pre-print, etc.  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：4

Number of peer-reviewed articles in Japanese journals：1

Proceedings of International Conference Number of peer-reviewed papers：0

Proceedings of domestic conference Number of peer-reviewed papers：0

Type：Peer review 

Number of peer-reviewed articles in foreign language journals：1

Number of peer-reviewed articles in Japanese journals：1

Type：Competition, symposium, etc. 

researchmap

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Research consultation

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Research consultation

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

Type：Lecture

researchmap

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Lecture

Audience： General,　Scientific,　Company,　Civic organization,　Governmental agency

Type：Seminar, workshop

Type：Seminar, workshop

researchmap